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A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations.
NCT05355701 · Pfizer
In plain English
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Official title
A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTI TUMOR ACTIVITY OF PF-07799933 (ARRY-440) AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS 16 YEARS AND OLDER WITH ADVANCED SOLID TUMORS WITH BRAF ALTERATIONS
About this study
The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called PF-07799933) administered as a single agent and in combination with other study medicines in people with solid tumors.
This study is seeking participants who have an advanced solid tumor with a certain type of abnormal gene called "BRAF" and available treatments are no longer effective in controlling their cancer.
All participants in this study will receive PF-07799933. PF-07799933 comes as a tablet to take by mouth, 2 times a day. Depending on the part of the study, participants may also receive another study medicine:
* People with melanoma or other solid tumors may also receive binimetinib. Binimetinib comes as a tablet to take by mouth, 2 times a day.
* People with colorectal cancer may also receive cetuximab or cetuximab and mFOLFOX6 (Chemotherapy regimen). Cetuximab will be given weekly (or every two weeks) in the clinic as a shot given in the vein or port (intravenous, IV).
Participants may receive the study medicines for about 2 years. The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.
Eligibility criteria
This study is seeking participants who meet the following key eligibility criteria:
Inclusion Criteria:
* Diagnosis of advanced/metastatic solid tumor including primary brain tumor.
* Qualifying BRAF alteration (V600 or non-V600 Class II/Class III BRAF alteration), in tumor tissue and/or blood (ie circulating tumor deoxyribonucleic acid \[DNA\], or ctDNA).
* Disease progressed during/following last prior treatment and no satisfactory alternative treatment options (Part 1, Part 2 (doublet), and Part 3 (cohorts 2, 3, 6, 7)).
* Tumor specific cohorts (melanoma, colorectal cancer) must have received specific prior approved therapies
* Part 3 (Cohort 1) (BRAF V600 mutant melanoma): Prior BRAF V600 inhibitor therapy required, prior MEK inhibitor therapy required, and immune checkpoint inhibitor therapy required.
* Part 3 (Cohort 4) (BRAF V600E CRC): Minimum of 2 cycles of prior 5-FU based chemotherapy required. No prior BRAF inhibitor/EGFR inhibitor allowed. Participants with MSI-H/dMMR mCRC should receive prior immune checkpoint inhibitor therapy.
* Part 3 (Cohort 5) (BRAF V600E CRC): No more than 2 cycles of prior 5-FU based chemotherapy allowed. No prior BRAF inhibitor/EGFR inhibitors allowed. Participants with MSI-H/dMMR mCRC should receive prior immune checkpoint inhibitor therapy.
Exclusion Criteria:
* Brain metastasis larger than 4 cm
* Systemic anti-cancer therapy or small molecule therapeutics ongoing at the start of study treatment.
* History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO; history of retinal degenerative disease.
* Concurrent neuromuscular disorder associated with elevated creatine kinase (CK).
Study design
Enrollment target: 267 participants
Allocation: non_randomized
Masking: none
Age groups: child, adult, older_adult
Timeline
Starts: 2022-07-05
Estimated completion: 2030-05-06
Last updated: 2026-03-27
Interventions
Drug: PF-07799933Drug: binimetinibBiological: cetuximabDrug: midazolamDrug: fluorouracilDrug: leucovorinDrug: oxaliplatin
Primary outcomes
- • Number of participants with dose limiting toxicities (DLTs) (Part 1 and Part 2) (Cycle 1 (21 days))
- • Number of participants with treatment-emergent adverse events (AEs) (Part 1 and Part 2) (Baseline to 28 days after last dose of study medication)
- • Number of participants with clinically significant change from baseline in laboratory abnormalities (Part 1 and Part 2) (Baseline to 28 days after last dose of study treatment)
Sponsor
Pfizer · industry
Contacts & investigators
ContactPfizer CT.gov Call Center · contact · ClinicalTrials.gov_Inquiries@pfizer.com · 1-800-718-1021
InvestigatorPfizer CT.gov Call Center · study_director, Pfizer
All locations (41)
Highlands Oncology GroupRecruiting
Fayetteville, Arkansas, United States
Highlands Oncology GroupRecruiting
Rogers, Arkansas, United States
Highlands Oncology GroupRecruiting
Springdale, Arkansas, United States
Clinical and Translational Research Center (CTRC)Recruiting
Aurora, Colorado, United States
UCHealth Sue Anschutz-Rodgers Eye CenterRecruiting
Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)Recruiting
Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)Recruiting
Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)Recruiting
Aurora, Colorado, United States
Sylvester Comprehensive Cancer CenterRecruiting
Miami, Florida, United States
University of Miami Hospital and ClinicsRecruiting
Miami, Florida, United States
Brigham and Women's HospitalRecruiting
Boston, Massachusetts, United States
Dana-Farber Cancer InstituteRecruiting
Boston, Massachusetts, United States
DFCI Chestnut HillRecruiting
Newton, Massachusetts, United States
Brigitte Harris Cancer PavilionRecruiting
Detroit, Michigan, United States
Henry Ford HospitalRecruiting
Detroit, Michigan, United States
Henry Ford Medical Center - ColumbusRecruiting
Novi, Michigan, United States
CT Scan and Echo Only: Henry Ford Medical Center-PlymouthRecruiting
Plymouth, Michigan, United States
MSK MonmouthRecruiting
Middletown, New Jersey, United States
MSK David H. Koch Center for Cancer CareRecruiting
New York, New York, United States
Memorial Sloan Kettering Cancer Center 53rd streetRecruiting
New York, New York, United States
Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
Cleveland Clinic Taussig Cancer Center Investigational PharmacyRecruiting
Cleveland, Ohio, United States
Cleveland ClinicRecruiting
Cleveland, Ohio, United States
Providence Cancer Institute Franz ClinicRecruiting
Portland, Oregon, United States
Providence Portland Medical CenterRecruiting
Portland, Oregon, United States
Sarah Cannon Research Institute - PharmacyRecruiting
Nashville, Tennessee, United States
SCRI Oncology PartnersRecruiting
Nashville, Tennessee, United States
TriStar Bone Marrow TransplantRecruiting
Nashville, Tennessee, United States
TriStar Centennial Medical Center - Cell Processing LabRecruiting
Nashville, Tennessee, United States
TriStar Centennial Medical centerRecruiting
Nashville, Tennessee, United States
START San AntonioRecruiting
San Antonio, Texas, United States
Cross Cancer InstituteNot Yet Recruiting
Edmonton, Alberta, Canada
The Ottawa Hospital - General CampusRecruiting
Ottawa, Ontario, Canada
University Health NetworkRecruiting
Toronto, Ontario, Canada
Princess Margaret Cancer CentreRecruiting
Toronto, Ontario, Canada
Jewish General HospitalRecruiting
Montreal, Quebec, Canada
McGill University Health CentreRecruiting
Montreal, Quebec, Canada
Sheba Medical CenterRecruiting
Ramat Gan, Central District, Israel
Sourasky Medical CenterRecruiting
Tel Aviv, Central District, Israel
Hadassah Medical CenterRecruiting
Jerusalem, Jerusalem, Israel
Rambam Health Care CampusRecruiting
Haifa, Ḥeifā, Israel